We conducted this study to determine the prevalence of elevated erythrocyte sedimentation rate (ESR) in chronic hemodialysis patients and to evaluate the dialytic and serum factors that might explain this elevation. ESR was measured using the Westergren method immediately before and immediately after dialysis sessions in 200 stable (i.e. with no other obvious systemic illnesses) hemodialysis patients and in 50 hemodialysis patients during concurrent acute illnesses. ESR was found to be > 25 mm/h in 180 (90%) patients, >50 mm/h in 76 (38%) and > 100 mm/h in 64(32%) patients. The mean pre dialysis ESR was not significantly different from the mean post dialysis ESR (77 ± 38 Vs 78 ± 35 mm/h, respectively). The mean ESR in the 50 patients during acute illnesses was not significantly different from the mean ESR measured during the stable state. Among all dialytic, biochemical and serum factors that were studied in this population, fibrinogen was the only factor that independently correlated significantly with ESR (P=0.015). In conclusion, this study showed that our dialysis patients had a tendency for elevated ESR and almost one third of them (32%) had ESR >100 in the absence of malignancy or other clinical factors known to cause such levels. There was a significant correlation between elevated ESR and fibrinogen level. Thus, an ESR of > 100 does not necessarily warrant extensive investigations for causes other than the renal failure/hemodialysis state unless other indicators exist to justify the search.

Keywords: Dialysis, Erythrocyte sedimentation, Fibrinogen

How to cite this article:Al-Homrany M. The Significance of Extreme Elevation of the Erythrocyte Sedimentation Rate in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2002;13:141-5

Since 1921, when Fahraeus first described the accelerated rate of erythrocyte sedimen­tation in pregnant women, this simple test has served as a nonspecific indicator of the presence of disease.[1] It also has been found useful in monitoring response to therapy, especially in rheumatologic diseases. Although the erythrocyte sedimentation rate (ESR) is a nonspecific test, there is a general impression that markedly elevated ESRs may have greater diagnostic specificity. Indeed, since Zacharski and Kyle[2] reported from the Mayo Clinic that 58% of the patients with ESR of over 100 mm/hr had underlying malignant disease, many physicians have felt obliged to undertake extensive diagnostic evaluation in patients found to have extremely high ESR. Extreme elevation (≥100 mm/hr) was found in several conditions including malignancies, infection and collagen vascular diseases.[3]

The value of measuring ESR in renal patients is not clear in the literature and early reports suggested that 1-17% of the patients with extremely elevated ESR (>100 mm/hr) had renal diseases of varying etiologies.[2],[3],[4] Such data on the dialysis population are scanty and inconclusive.[5],[6] We conducted this study to evaluate the range of elevated ESR in stable hemodialysis patients who do not have underlying diseases that may elevate the ESR, to study the effect of hemodialysis on the ESR, to detect factors that may contribute to the elevated ESR and to study the effect of acute illnesses on the baseline ESR in dialysis patients.

Material and Methods

We selected consecutive regular hemo­dialysis patients attending the outpatient dialysis center in Abha, Saudi Arabia, from March 1999 to December 1999 were selected.

Patients with conditions that are known to influence the measurement of ESR were excluded, such as acute or chronic infection, malignancy, connective tissue diseases, history of recent surgery, pregnancy and drugs: In particular the drugs excluded were non-steroidal anti-inflammatory drugs, aspirin and antihistamines.

The ESR was measured both immediately before and immediately after dialysis sessions. Six months later, the ESR was repeated in all available patients receiving dialysis to determine variability over time. ESR was also measured in 50 such patients who developed acute illnesses and required hospitalization for diseases such as: tuber­culosis, pneumonia, sepsis etc.

All patients were dialyzed three times per week using a C10 cuprophan dialyzer. ESR was measured using modified Westergren method. Blood was collected undiluted in an EDTA tube and transferred to standard 20 cm Westergren tube within two hours of being drawn. Blood was allowed to settle at room temperature in a vertical column and one reading was obtained after one hour. Elevated ESR was defined as ESR ?25 mm/h.

Statistical analysis

Data were analyzed using SPSS software. Data presented here are expressed as the mean ± SE. Differences in the mean ESRs between identical patient groups at different times were analyzed by Wilkinson's test.

Correlation between the ESR and categorical values was assessed by using the "t" and one-way ANOVA tests. Spearman's test was used to assess the correlation between the ESR and continuous variables. Multiple regression analysis was used to relate the ESR to the variables showing significant correlation with spearman's test. Statistical significance was set as P values of <0.05.

Results

A total of 200 patients were studied; 104 (52%) males and 96 (48%) females with a mean age of 49.8 ± 17.1 years (range 13 to 90 years). The mean duration on dialysis was 26 ± 5 month (range 3-130 months). Causes of end-stage renal disease (ESRD) are shown in [Table - 1]. Chronic glomerulonephritis was diagnosed in 108 (54%) patients followed by "unknown etiology" in 48 (24%) patients.

Alteration in the sedimentation rate has been attributed to both plasma and red blood cell factors.[6] The ESR is directly proportional to the mass of the erythrocytes and inversely proportional to the surface area, which carries the negative charge that prevents aggregation. Large cells have a small surface­to-volume ratio and less charge in relation to their mass than microcytes. Thus, macrocytes sediment more rapidly than normal cells while microcytes sediment more slowly.[7] Since erythrocyte aggregation is caused by electrostatic forces,[8] these cells normally have a net negative charge and repel each other. Many plasma proteins including fibrinogen are positively charged and neutralize the surface charge of erythrocytes, thereby reducing the repulsive forces and promoting aggregation (rouleaux formation).[8]

Some plasma proteins are known as acute phase reactants and facilitate erythrocyte aggregation.[8] These proteins include fibri­nogen, β-globulin, ∞1-globulin, γ-globulin and albumin. Age, sex, anemia and some drugs (such as salicylates, anti-inflammatory drugs, anti-histamines) are known factors that affect sedimentation in non-uremic individuals.[7],[8]

In uremic patients the mechanism of the elevated ESR was not fully explained and multiple factors such as: age, hemoglobin level, hypocalcemia and elevated fibrinogen are probably involved.[5],[6] Our findings confirmed the earlier reports that most stable dialysis patients have significant acceleration of ESR (90%).[ 5],[6] Among all factors that are known to influence the acceleration, fibrinogen was the only factor in our study that correlated significantly and independently, with the ESR. Indeed, the quantity and the activity of fibrinogen was shown to be significantly elevated in uremic patients when compared with the healthy controls.[9]

Although the majority of our patients were anemic, our results failed to show any correlation between the ESR and anemia. There is no clear explanation for such a finding; however, it is possible that the effect of hemoglobin is weaker than fibrinogen. In addition, the size of erythrocytes in renal failure patients is typically normocytic.

Furthermore, the present report in contrast to previous studies[5],[6] did not show any significant correlation between the elevated ESR and age or gender of the patients. The possible correlation of the elevated ESR in dialysis patients with the chronic inflam­matory response to the bioincompatible membranes need to be further confirmed in patients using more biocompatible dialyzers or in patients using peritoneal dialysis as a renal replacement therapy.

In conclusion, this study showed that our dialysis patients had a general tendency for elevated ESR (>25 in 90% of patients) and almost one third of them (32%) had ESR >100 in the absence of malignancy or other clinical factors known to cause such levels. There was a significant correlation between elevated ESR and fibrinogen level. Thus, an ESR of ≥100 does not necessarily warrant extensive investigations for causes other than the renal failure/hemodialysis state unless other indicators exist to justify the search.

Acknowledgement

I would like to thank Prof. Abulfotoh and Prof. Ahmed for reviewing the manuscript and helping in the statistical analysis. Also I appreciate the Secretarial assistance of Mr. Syed Rashid Sami.